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Scientific result | Diagnosis and innovative treatment | Positron Emission Tomography
Personalized medicine approaches in radiotherapy tend to deliver a radiation dose adapted to each patient and each tumor. Nanoparticles (NP) called "radio-enhancers" can increase the effectiveness of radiotherapy while preserving healthy tissue. Researchers from the BioMaps laboratory (SHFJ) and the Institut des Sciences Moléculaires d'Orsay (ISMO) have demonstrated in vivo that platinum (Pt) nanoparticles could be such radiosensitizing agents. They determined their pharmacokinetics by PET imaging.
Radiotherapy is a key treatment in oncology. Approximately 50% of all cancer patients receive it. The total dose of radiation delivered to the tumor, as well as the tolerance of the surrounding normal tissues affected during the radiotherapy session, greatly influences its effectiveness.
There is a growing interest in metallic nanoparticles containing atoms with a high atomic number (Z) (high-Z based nanoparticles) as potential radiosensitizers (nano-radio-enhancers NRE). "Activated" by the radiation used in radiotherapy, they amplify the effects of the radiation locally. Thanks to their specific accumulation in solid tumors due to their biological properties (mainly a large vascular network and weak lymphatic drainage), a phenomenon known as the EPR (Enhanced Permeation and Retention) effect, these radiosensitizing nanoparticles make it possible to increase the effectiveness of radiotherapy while preserving healthy tissue.
Most of the nanoparticles under development or in clinical trials contain gold, gadolinium or hafnium because of their low toxicity and high amplification potential. Researchers from the BioMaps laboratory (SHFJ) and the Institut des Sciences Moléculaires d'Orsay (ISMO) have demonstrated in vitro that platinum (Pt) nanoparticles could also be an interesting alternative.
In the present study (published in Nanomedicine: NBM), they radiolabeled these Pt-based nanoparticles and used positron emission tomography (PET) to analyze their behavior in vivo. The objective was to characterize the associated RPE effect. This effect could be very heterogeneous between two patients, or even between the different tumor lesions of the same patient. Its precise determination should allow to define precisely the specific doses of ionizing radiation for an irradiation session and thus to improve safety. They chose to conduct this study in an animal model of melanoma, a very aggressive cancer that is difficult to cure with conventional therapy.
The combination of Pt nanoparticles and irradiation significantly improved the efficacy of the radiotherapy. PET imaging revealed an impressive tumor accumulation of the nanoparticles which can be explained by their size (around 30 nm). This accumulation, sustained in the peripheral and highly proliferative part of the tumor, is all the more beneficial since tumor cell proliferation is one of the main causes of local failure of radiotherapy. The persistence of the nanoparticles in the tumor should make it possible to perform several successive treatment sessions without the need for multiple injections of the nanoparticles.
Thanks to their nano-PET imaging method, BioMaps and ISMO researchers are able to quantify the heterogeneous RPE effect. This precise quantification of the nanoparticle distribution should help predict the effect of NPs to perform personalized radiotherapy and thus improve patient management. Their platinum nanoparticle-based ERN shows promising results in terms of biocompatibility and accumulation in the tumor and is suitable for the field of theranostics.
In order to make it attractive, the next step will be to correlate pharmacokinetic data with the efficacy of radiotherapy in vivo.
Vu Long Tran, Hynd Remita, Farah Savina,
Benoit Jego, Sandrine Lacombe, Erika Porcel,
Pharmacokinetics derived from PET imaging of inspiring radio-enhancer platinum nanoparticles Nanomedicine: NBM 2022, https://doi.org/10.1016/j.nano.2022.102603
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